1. Field of the Invention
The invention relates to a process for the regioselective N-alkylation of 2-alkyl-5,6,7 or 8-substituted-4(3H)-quinazolinones in the presence of lithium salts to give 2-alkyl-3-substituted-5,6,7 or 8-substituted-4(3H)-quinazolinones. This process has the advantages of providing a high yield of purer product in a more efficient and less costly way.
2. Description of the Prior Art
The compounds prepared by the process of the present invention namely the 2-alkyl-3-substituted-5,6,7 or 8-substituted-4(3H)-quinazolinones compounds of the following Formula I: ##STR1## where R.sup.1, R.sup.2 and X are defined hereinafter, are important intermediates useful in the preparation of therapeutic 2,3,6-substituted quinazolinones which are useful as angiotensin II receptor blocking agents. The 2,3,6-substituted quinazolinone compounds and uses for such compounds are described in European Patent Application No. EP-497150-A.
As described in this application, the usual method used to prepare these 3-substituted quinazolinones involves reacting compounds of the formula: ##STR2## where R.sup.1, and X are defined hereinafter, with an alkylating agent of the formula: R.sup.2 Br, where R.sup.2 is as defined hereinafter, in the presence of bases such as potassium or sodium carbonate or potassium t-butoxide. However, a significant amount of the isomeric O-alkylated compound of the formula: ##STR3## where R.sup.1, R.sup.2 and X are defined hereinafter, is formed and is in many cases difficult to remove from the desired product.
Accordingly, this prior art process for the preparation of 2-alkyl-3-substituted-6-substituted-4(3H)-quinazolinones generally give rise to appreciable quantities of undesired by-products.
It has now been found that 2-alkyl-3-substituted-5,6,7 or 8-substituted-4(3H)-quinazolinone compounds may be advantageously synthesized via reaction of the appropriate alkylating reagent in the presence of lithium salts to produce the desired N-alkylated product without the presence of O-alkylated contaminates.